Title:
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Genetic Diversity of Plasmodium Vivax Metacaspase 1 and Plasmodium Vivax Multi-Drug Resistance 1 Genes of Field Isolates From Mauritania, Sudan and Oman |
Author:
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Sow, Fatimata; Bonnot, Guillaume; Ahmed, Bilal Rabah; Diagana, Sidi Mohamed; Kebe, Hachim; Koita, Mohamedou; Samba, Ba Malado; Almukhaini, Said K.; Alzadjali, Majed; Alabri, Seif S.; Ali, Osama A. M.; Samy, Abdallah M.; Abdelhamid, Muzamil Mahdi; Albsheer, Musab M. Ali; Simon, Bruno; Bienvenu, Anne‑Lise; Petersen, Eskild; Picot, Stéphane
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Abstract:
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Background: Plasmodium vivax is the second most important human malaria parasite, widely spread across the
world. This parasite is associated with important issues in the process toward malaria elimination, including potential
for relapse and increased resistance to chloroquine. Plasmodium vivax multi‑drug resistant (pvmdr1) is suspected to be
a marker of resistance although definitive evidence is lacking. Progress has been made in knowledge of biological factors
affecting parasite growth, including mechanisms of regulated cell death and the suspected role of metacaspase.
Plasmodium vivax metacaspase1 (PvMCA1‑cd) has been described with a catalytic domain composed of histidine
(H372) and cysteine (C428) residues. The aim of this study was to test for a link between the conserved histidine and
cysteine residues in PvMCA1‑cd, and the polymorphism of the P. vivax multi‑drug resistant gene (pvmdr1).
Results: Thirty P. vivax isolates were collected from Mauritania, Sudan, and Oman. Among the 28 P. vivax isolates successfully
sequenced, only 4 samples showed the conserved His (372)–Cys (428) residues in PvMCA1‑cd. Single nucleotide
polymorphisms observed were H372T (46.4%), H372D (39.3%), and C428R (85.7%). A new polymorphic catalytic
domain was observed at His (282)–Cys (305) residues. Sequences alignment analysis of pvmdr1 showed SNP in the
three codons 958, 976 and 1076. A single SNP was identified at the codon M958Y (60%), 2 SNPs were found at the
position 976: Y976F (13%) and Y976V (57%), and 3 SNPs were identified at the position 1076: F1076L (40%), F1076T
(53%) and F1076I (3%). Only one isolate was wildtype in all three codons (MYF), 27% were single MYL mutants, and
10% were double MFL mutants. Three new haplotypes were also identified: the triple mutant YVT was most prevalent
(53.3%) distributed in the three countries, while triple YFL and YVI mutants (3%), were only found in samples
from Sudan and Mauritania.
Conclusions: Triple or quadruple mutants for metacaspase genes and double or triple mutants for Pvmdr1 were
observed in 24/28 and 19/28 samples. There was no difference in the frequency of mutations between PvMCA1‑
cd and Pvmdr1 (P > 0.2). Histidine and cysteine residues in PvMCA1‑cd are highly polymorphic and linkage |
URI:
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http://khartoumspace.uofk.edu/123456789/25109
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